Neurobiology: Neuropeptides go out on a limb.

Autotomy happens when an animal divests itself of an appendage in the interests of survival. A serendipitous observation shows that a sulfakinin/cholecystokinin-type neuropeptide promotes autotomy in starfish, opening a new route to understanding this fascinating phenomenon.

Getting around the roundworms: Identifying knowledge gaps and research priorities for the ascarids.

The ascarids are a large group of parasitic nematodes that infect a wide range of animal species. In humans, they cause neglected diseases of poverty; many animal parasites also cause zoonotic infections in people. Control measures include hygiene and anthelmintic treatments, but they are not always appropriate or effective and this creates a continuing need to search for better ways to reduce the human, welfare and economic costs of these infections.

Modelling organophosphate intoxication in C. elegans highlights nicotinic acetylcholine receptor determinants that mitigate poisoning.

Organophosphate intoxication via acetylcholinesterase inhibition executes neurotoxicity via hyper stimulation of acetylcholine receptors. Here, we use the organophosphate paraoxon-ethyl to treat C. elegans and use its impact on pharyngeal pumping as a bio-assay to model poisoning through these neurotoxins.

PharmacoGenetic targeting of a C. elegans essential neuron provides an in vivo screening for novel modulators of nematode ion channel function.

Chemical or drug treatments are successfully used to treat parasitic nematode infections that impact human, animal and plant health. Many of these exert their effects through modifying neural function underpinning behaviours essential for parasite viability. Selectivity against the parasite may be achieved through distinct pharmacological properties of the parasite nervous system, as exemplified by the success of the ivermectin which target a glutamate-gated chloride channel found only in invertebrates.

Confounds of using the unc-58 selection marker highlights the importance of genotyping co-CRISPR genes.

Multiple advances have been made to increase the efficiency of CRISPR/Cas9 editing using the model genetic organism Caenorhabditis elegans (C. elegans). Here we report on the use of co-CRISPR 'marker' genes: worms in which co-CRISPR events have occurred have overt, visible phenotypes which facilitates the selection of worms that harbour CRISPR events in the target gene.

Development of emodepside as a possible adulticidal treatment for human onchocerciasis-The fruit of a successful industrial-academic collaboration.

Current mass drug administration (MDA) programs for the treatment of human river blindness (onchocerciasis) caused by the filarial worm Onchocerca volvulus rely on ivermectin, an anthelmintic originally developed for animal health. These treatments are primarily directed against migrating microfilariae and also suppress fecundity for several months, but fail to eliminate adult O. volvulus.

Impact of drug solvents on pharyngeal pumping.

provides a multi-cellular model organism for toxicology and drug discovery. These studies usually require solvents such as dimethyl sulfoxide (DMSO), ethanol or acetone as a vehicle. This raises the need to carefully consider whether the chemical vehicles used in these screens are anodyne towards .

Investigating autism associated genes in C. elegans reveals candidates with a role in social behaviour.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a triad of behavioural impairments and includes disruption in social behaviour. ASD has a clear genetic underpinning and hundreds of genes are implicated in its aetiology. However, how single penetrant genes disrupt activity of neural circuits which lead to affected behaviours is only beginning to be understood and less is known about how low penetrant genes interact to disrupt emergent behaviours.

Neuroligin dependence of social behaviour in Caenorhabditis elegans provides a model to investigate an autism-associated gene.

Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neuroligin in social circuitry and the impact of genetic variation to this gene is not fully understood.

C. elegans pharyngeal pumping provides a whole organism bio-assay to investigate anti-cholinesterase intoxication and antidotes.

Inhibition of acetylcholinesterase by either organophosphates or carbamates causes anti-cholinesterase poisoning. This arises through a wide range of neurotoxic effects triggered by the overstimulation of the cholinergic receptors at synapses and neuromuscular junctions. Without intervention, this poisoning can lead to profound toxic effects, including death, and the incomplete efficacy of the current treatments, particularly for oxime-insensitive agents, provokes the need to find better antidotes.

Identification and characterisation of serotonin signalling in the potato cyst nematode Globodera pallida reveals new targets for crop protection.

Plant parasitic nematodes are microscopic pathogens that invade plant roots and cause extensive damage to crops. We have used a chemical biology approach to define mechanisms underpinning their parasitic behaviour: We discovered that reserpine, a plant alkaloid that inhibits the vesicular monoamine transporter (VMAT), potently impairs the ability of the potato cyst nematode Globodera pallida to enter the host plant root. We show this is due to an inhibition of serotonergic signalling that is essential for activation of the stylet which is used to access the host root.

Report on the First Symposium on Invertebrate Neuroscience held on 13-17th August 2019 at the Balaton Limnological Institute, MTA Centre for Ecological Research, Tihany, Hungary.

This meeting report provides an overview of the oral and poster presentations at the first international symposium for invertebrate neuroscience. The contents reflect the contributions of invertebrate neuroscience in addressing fundamental and fascinating challenges in understanding the neural substrates of animal behaviour.

The distinct profiles of the inhibitory effects of fluensulfone, abamectin, aldicarb and fluopyram on Globodera pallida hatching.

Background: Fluensulfone is a nematicide with a novel mode of action against plant parasitic nematodes. Here, we utilize in vitro hatching assays to investigate fluensufone's ability to inhibit Globodera pallida hatching, relative to the efficacy of other distinct classes of nematicides.

Results: Fluensulfone, abamectin, aldicarb and fluopyram inhibit G.

Intra Strain Variation of the Effects of Gram-Negative ESKAPE Pathogens on Intestinal Colonization, Host Viability, and Host Response in the Model Organism .

In its native environment of rotting vegetation, the soil nematode encounters a range of bacteria. This includes species from the ESKAPE group of pathogens that pose a clinical problem in acquired hospital infections. Here, we investigated three Gram-negative members of the ESKAPE group, , , and .

The cysteine-string protein homologue DNJ-14 is dispensable for neuromuscular junction maintenance across ageing.

Maintenance of synaptic function across ageing is vital in sustaining cognitive function. Synaptic dysfunction is a key part of the pathophysiology of a number of neurodegenerative diseases. The synaptic co-chaperone, cysteine-string protein (CSP), is important for synaptic maintenance and function in , mice and humans, and disruption of CSP results in synaptic degeneration.

Neuroligin tuning of pharyngeal pumping reveals extrapharyngeal modulation of feeding in .

The integration of distinct sensory modalities is essential for behavioural decision making. In , this process is coordinated by neural circuits that integrate sensory cues from the environment to generate an appropriate behaviour at the appropriate output muscles. Food is a multimodal cue that impacts the microcircuits to modulate feeding and foraging drivers at the level of the pharyngeal and body wall muscle, respectively.

Invertebrate models of behavioural plasticity and human disease.

The fundamental processes of neural communication have been largely conserved through evolution. Throughout the last century, researchers have taken advantage of this, and the experimental tractability of invertebrate animals, to advance understanding of the nervous system that translates to mammalian brain. This started with the inspired analysis of the ionic basis of neuronal excitability and neurotransmission using squid during the 1940s and 1950s and has progressed to detailed insight into the molecular architecture of the synapse facilitated by the genetic tractability of the nematode and the fruit fly .

Yeast two-hybrid screening identifies MPZ-1 and PTP-1 as candidate scaffolding proteins of metabotropic glutamate receptors in Caenorhabditis elegans.

The metabotropic glutamate receptors (mGluRs) are a class of G-protein-coupled receptor that undergo extensive interactions with scaffolding proteins, and this is intrinsic to their function as an important group of neuromodulators at glutamatergic synapses. The Caenorhabditis elegans nervous system expresses three metabotropic glutamate receptors, MGL-1, MGL-2 and MGL-3. Relatively little is known about how the function and signalling of these receptors is organised in C.

Investigation of feeding behaviour in C. elegans reveals distinct pharmacological and antibacterial effects of nicotine.

Caenorhabditis elegans is an informative model to study the neural basis of feeding. A useful paradigm is one in which adult nematodes feed on a bacterial lawn which has been pre-loaded with pharmacological agents and the effect on pharyngeal pumping rate scored. A crucial aspect of this assay is the availability of good quality bacteria to stimulate pumping to maximal levels.

Deciphering the molecular determinants of cholinergic anthelmintic sensitivity in nematodes: When novel functional validation approaches highlight major differences between the model Caenorhabditis elegans and parasitic species.

Cholinergic agonists such as levamisole and pyrantel are widely used as anthelmintics to treat parasitic nematode infestations. These drugs elicit spastic paralysis by activating acetylcholine receptors (AChRs) expressed in nematode body wall muscles. In the model nematode Caenorhabditis elegans, genetic screens led to the identification of five genes encoding levamisole-sensitive-AChR (L-AChR) subunits: unc-38, unc-63, unc-29, lev-1 and lev-8.

The long and the short of it - a perspective on peptidergic regulation of circuits and behaviour.

Neuropeptides are the most diverse class of chemical modulators in nervous systems. They contribute to extensive modulation of circuit activity and have profound influences on animal physiology. Studies on invertebrate model organisms, including the fruit fly and the nematode , have enabled the genetic manipulation of peptidergic signalling, contributing to an understanding of how neuropeptides pattern the output of neural circuits to underpin behavioural adaptation.

Progressive metabolic impairment underlies the novel nematicidal action of fluensulfone on the potato cyst nematode Globodera pallida.

Background: Fluensulfone is a new nematicide with an excellent profile of selective toxicity against plant parasitic nematodes. Here, its effects on the physiology and biochemistry of the potato cyst nematode Globodera pallida have been investigated and comparisons made with its effect on the life-span of the free-living nematode Caenorhabditis elegans to provide insight into its mode of action and its selective toxicity.

Results: Fluensulfone exerts acute effects (≤1h; ≥100μM) on stylet thrusting and motility of hatched second stage G.

An oxytocin-dependent social interaction between larvae and adult C. elegans.

Oxytocin has a conserved role in regulating animal social behaviour including parental-offspring interactions. Recently an oxytocin-like neuropeptide, nematocin, and its cognate receptors have been identified in the nematode Caenorhabditis elegans. We provide evidence for a pheromone signal produced by C.